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Abstract Background Fluoroquinolone resistance is an issue of concern amongst physicians worldwide. In urology, fluoroquinolones are often used in the treatment of acute pyelonephritis and prostatitis, as well as infections caused by multidrug‐resistant pathogens. Aims We aim to highlight the importance of antimicrobial stewardship and the need for ongoing biomedical research to discover novel agents in our losing battle against resistant pathogens. Materials and methods In this review, we survey the literature and summarise fluoroquinolone resistance as it pertains to pyelonephritis and prostatitis, as well as alternative treatment strategies and prevention of multidrug resistance. Results The rise of fluoroquinolone resistance in bacteria has reduced the available treatment options, often necessitating hospital admission for intravenous antibiotics, which places an additional burden on both patients and the healthcare system. Many countries such as Australia have attempted to limit fluoroquinolone resistance by imposing strict prescribing criteria, though these efforts have not been entirely successful. Solutions to overcome resistance include prevention, combination therapy and the development of novel antimicrobial agents. Conclusions Prevention of the proliferation of resistant organisms by antimicrobial stewardship is paramount, and urologists are obliged to be aware of responsible prescribing practices such as referring to local guidelines when prescribing. By reserving fluoroquinolones for infections in which they are truly indicated and by prescribing based on both patient and local environmental factors, we can preserve this effective resource for future use.

An 89-year-old woman with paroxysmal atrial tachycardia (AT) was diagnosed with severe atrial functional mitral regurgitation. On transesophageal echocardiography, the mitral regurgitation jet appeared larger during sinus rhythm and smaller during AT. During transcatheter repair of the valve, chronotropic agents were given to induce AT, assisting with leaflet capture.

Finasteride competitively inhibits 5α-reductase (5-AR) isoenzymes, which blocks dihydrotestosterone (DHT) production, thereby reducing DHT. Finasteride is used in the management of benign prostatic hyperplasia (BPH) and androgenic alopecia. Amid patient reports of suicidal ideation (SI), the Post Finasteride Syndrome advocacy group has petitioned for either a stop to selling of the drug or advertisement of stronger warnings. The US Food and Drug Administration recently added SI to the adverse effects listed for finasteride. Here we provide a brief but comprehensive review of the literature on the psychological side effects of 5-AR inhibitors (5-ARIs) to provide an opinion to help in guiding treating urologists. Most of the current evidence, obtained from the literature on dermatology, suggests that 5-ARI users experience a higher rate of depressive symptoms. However, given the lack of comprehensive randomised studies, the causal link between finasteride and SI remains unclear. Urologists prescribing 5-ARIs should be aware of the recent addition of suicide and SI risk to the list of side effects. A mental health screen should be performed and appropriate resources provided to patients commencing treatment. Furthermore, a review should be arranged with the general practitioner to assess new-onset mental health or SI symptoms. Patient summary: We provide recommendations for urologists who prescribe finasteride for the treatment of benign prostate enlargement. Urologists should be aware of the recent addition of suicidal ideation to the list of side effects for this drug. Finasteride prescription should be continued; however, we recommend a detailed medical history to screen for prior mental health and personality disorders, with discontinuation of the medication in patients with new onset of depression or suicidal symptoms. Close liaison with the patient’s general practitioner is vital for management of depressive or suicidal symptoms.

# Background Intrinsic foot muscle (IFM) weakness can result in reduced foot function, making it crucial for clinicians to track IFM strength changes accurately. However, assessing IFM strength can be challenging for clinicians, as there is no clinically applicable direct measure of IFM strength that has been shown to be reliable and valid with the foot on the ground. # Purpose The purpose was to investigate the intra-rater and inter-rater reliability of a novel, budget-friendly IFM dynamometer and determine its agreement with a handheld dynamometer (HHD). The researchers also examined correlations of foot morphology and activity level to IFM strength. # Study design Descriptive Laboratory Study # Methods Two assessors measured IFM strength of 34 healthy volunteers (4 male, 30 female; age=21.14±2.57, height=164.66 ±7.62 cm, mass=64.45±11.93 kg) on two occasions 6.62±0.78 days apart with the novel dynamometer to assess intra- and inter-rater reliability. The HHD was used to measure IFM in the first session in order to assess validity. # Results For the novel dynamometer, intra- and inter-rater reliability was moderate-to-excellent (ICC = 0.73 -- 0.95), and the majority of the strength tests were within the 95% limits of agreement with the HHD. Wider foot morphology and a higher number of days walking over the prior seven days had small but significant correlations with IFM strength (dominant foot r = 0.34, non-dominant foot r = 0.39; r = -0.33, -0.39 respectively). # Conclusion This novel IFM dynamometer is a budget-friendly (\$75) tool that was shown to be reliable and valid in a healthy population. # Levels of evidence Level 3

There has been an increasing demand for healthcare analytics skills and competence by healthcare organizations. Although many universities have established programs and courses on healthcare analytics, most of these curricula have been designed for information systems (IS), information technology (IT), or analytics students. It is unclear how these curricula would fit the needs of healthcare professionals who have little IT knowledge and background yet also need analytics for their clinical or administrative job roles. This research reports on the design of an executive MBA course intended for an audience of healthcare professionals. The learning objectives, topic coverage, software tools, and assessment methods are presented along with students' perceptions of these aspects of the course. Several important lessons learned are shared and future directions are proposed, which can help other educators design similar healthcare analytics courses for professional audiences.

The reliability of isokinetic peak torque (PT) has been reported mostly using a short-term (p ≤ 0.05) than those that involved sets two and three. Systematic error (p ≤ 0.05) was shown for 6 out of the 17 PT selection variables. On a subjective interpretation basis, when taking everything into account the best overall combination of time/trial efficiency, reliability, best/highest PT score parameter, and reduced risk of systematic bias appears to be the PT variable that uses the average of the highest two reps of the first two sets of three reps—i.e., averaging the highest two values of the six total reps from the first two sets.

Purpose: To determine the diagnostic parameters of breast ultrasound (US) in the setting of routine radiological surveillance after a diagnosis of breast cancer and evaluate costs of the inclusion of breast US as well as any survival benefit of US detected cases of recurrence in surveillance. Methods: 622 patients underwent breast cancer surgery and follow up at Austin Health from July 2009 to December 2015. Retrospective data analysis was performed to determine; diagnostic parameters, financial costs of US and survival outcomes of US detected cases of recurrence. Results: Patients underwent 1–9 years of breast cancer surveillance, with a median of 4.24 years. 390 (62.7%) patients underwent additional breast US surveillance to mammography. 232 (38.3%) fit criteria for use of additional breast US. 199 abnormal imaging episodes occurred, leading to 16 screen detected-cases of locoregional recurrence. US alone generated 107 abnormal images and found 9 cancers. US had a sensitivity of 44.1%, specificity of 95.2% and positive predictive value of 11.7% in comparison to mammography; 20.6%, 97.4% and 9.9% respectively. US had a biopsy rate of 4.0% and lead to an incremental cancer detection rate of 0.38%. The cost of incremental cancer found was $31,463.72 AUD. Survival outcomes based on method of detection of recurrence were insignificant (p value = 0.71). Conclusions: Breast US has a sensitivity of 44.1% and detected seven recurrences that were mammographically occult. Breast US has a similar PPV to mammography in surveillance. Breast US generated considerable biopsy rates and costs. Survival analysis was not able to detect any benefit of US detected cases of recurrence.

Efforts to create a sustainable hydrogen economy are gaining momentum as governments all over the world are investing in hydrogen production, storage, distribution, and delivery technologies to develop a hydrogen infrastructure. This involves transporting hydrogen in gaseous or liquid form or using carrier gases such as methane, ammonia, or mixtures of methane and hydrogen. Hydrogen is a colorless, odorless gas and can easily leak into the atmosphere leading to economic loss and safety concerns. Therefore, deployment of robust low-cost sensors for various scenarios involving hydrogen is of paramount importance. Here, we review some recent developments in hydrogen sensors for applications such as leak detection, safety, process monitoring in production, transport and use scenarios. The status of methane and ammonia sensors is covered due to their important role in hydrogen production and transportation using existing natural gas and ammonia infrastructure. This review further provides an overview of existing commercial hydrogen sensors and also addresses the potential for hydrogen as an interferent gas for currently used sensors. This review can help developers and users make informed decisions about how to drive hydrogen sensor technology forward and to incorporate hydrogen sensors into the various hydrogen deployment projects in the coming decade.

Background: Peripheral artery disease (PAD) is a complication of type 2 diabetes that leads to critical limb ischemia and amputation. We tested whether absent or diminished pedal pulses (ADPPs) predicts subsequent renal functional decline in patients with diabetic chronic kidney disease (CKD). We also examined the association between urinary biomarkers and ADPP as well as worsening CKD. Methods: Using a prospective longitudinal design, we studied 91 patients with type 2 diabetes and estimated glomerular filtration rate (eGFR) from 7 to 146 mL/min/1.73 m2. Baseline pedal pulses were assessed by standardized history and physical examination. The primary endpoint was decline in eGFR >30%. Potential confounders of the relationship between pedal pulses and eGFR were assessed by multivariable logistic regression. Results: Of 91 participants (median age 58 (range 30–83); median eGFR 72.4 ± 33.4 mL/min/1.73 m2), 43% had at least one ADPP. Baseline ADPP associated with increased risk of greater than 30% decline in eGFR (OR= 3.67, p = .004). This association remained significant (OR = 3.09, p = .029) after adjustment for traditional risk factors of renal function decline in diabetic kidney disease (DKD). In addition, urinary endothelin-1 (ET-1) was higher among patients with ADPP (p =.0006) and associated with eGFR decline greater than 30% (adjusted OR = 1.81, p = .035). Conclusions: ADPP is a strong predictor of decline in renal function in type 2 diabetes. Patients with type 2 diabetes and abnormal pedal pulses should be screened for DKD and monitored closely for progression of CKD.

ABSTRACT The phosphoserine/phosphothreonine-binding protein 14-3-3 is known to regulate actin; this function has been previously attributed to sequestration of phosphorylated cofilin. 14-3-3 was identified as an actin-associated protein in the deep-branching eukaryote Giardia lamblia; however, Giardia lacks cofilin and all other canonical actin-binding proteins (ABPs). Thus, the role of G. lamblia 14-3-3 (Gl-14-3-3) in actin regulation was unknown. Gl-14-3-3 depletion resulted in an overall disruption of actin organization characterized by ectopically distributed short actin filaments. Using phosphatase and kinase inhibitors, we demonstrated that actin phosphorylation correlated with destabilization of the actin network and increased complex formation with 14-3-3, while blocking actin phosphorylation stabilized actin filaments and attenuated complex formation. Giardia’s sole Rho family GTPase, Gl-Rac, modulates Gl-14-3-3’s association with actin, providing the first connection between Gl-Rac and the actin cytoskeleton in Giardia. Giardia actin (Gl-actin) contains two putative 14-3-3 binding motifs, one of which (S330) is conserved in mammalian actin. Mutation of these sites reduced, but did not completely disrupt, the association with 14-3-3. Native gels and overlay assays indicate that intermediate proteins are required to support complex formation between 14-3-3 and actin. Overall, our results support a role for 14-3-3 as a regulator of actin; however, the presence of multiple 14-3-3–actin complexes suggests a more complex regulatory relationship than might be expected for a minimalistic parasite. IMPORTANCE Giardia lacks canonical actin-binding proteins. Gl-14-3-3 was identified as an actin interactor, but the significance of this interaction was unknown. Loss of Gl-14-3-3 results in ectopic short actin filaments, indicating that Gl-14-3-3 is an important regulator of the actin cytoskeleton in Giardia. Drug studies indicate that Gl-14-3-3 complex formation is in part phospho-regulated. We demonstrate that complex formation is downstream of Giardia’s sole Rho family GTPase, Gl-Rac. This result provides the first mechanistic connection between Gl-Rac and Gl-actin in Giardia. Native gels and overlay assays indicate intermediate proteins are required to support the interaction between Gl-14-3-3 and Gl-actin, suggesting that Gl-14-3-3 is regulating multiple Gl-actin complexes.

The ability to selectively target disease-related tissues with molecules is critical to the design of effective therapeutic and diagnostic reagents. Recognizing the differences between the in vivo environment and in vitro conditions, we employed an in vivo selection strategy to identify RNA aptamers (targeting motifs) that could localize to tumor in situ. One of the selected molecules is an aptamer that binds to the protein DHX9, an RNA helicase that is known to be upregulated in colorectal cancer. Upon systemic administration, the aptamer preferentially localized to the nucleus of cancer cells in vivo and thus has the potential to be used for targeted delivery.

Task-based analysis of medical imaging performance underlies many ongoing efforts in the development of new imaging systems. In statistical image reconstruction, regularization is often formulated in terms to encourage smoothness and/or sharpness (e.g. a linear, quadratic, or Huber penalty) but without explicit formulation of the task. We propose an alternative regularization approach in which a spatially varying penalty is determined that maximizes task-based imaging performance at every location in a 3D image. We apply the method to model-based image reconstruction (MBIR—viz., penalized weighted least-squares, PWLS) in cone-beam CT (CBCT) of the head, focusing on the task of detecting a small, low-contrast intracranial hemorrhage (ICH), and we test the performance of the algorithm in the context of a recently developed CBCT prototype for point-of-care imaging of brain injury. Theoretical predictions of local spatial resolution and noise are computed via an optimization by which regularization (specifically, the quadratic penalty strength) is allowed to vary throughout the image to maximize local task-based detectability index (). Simulation studies and test-bench experiments were performed using an anthropomorphic head phantom. Three PWLS implementations were tested: conventional (constant) penalty; a certainty-based penalty derived to enforce constant point-spread function, PSF; and the task-based penalty derived to maximize local detectability at each location. Conventional (constant) regularization exhibited a fairly strong degree of spatial variation in , and the certainty-based method achieved uniform PSF, but each exhibited a reduction in detectability compared to the task-based method, which improved detectability up to ~15%. The improvement was strongest in areas of high attenuation (skull base), where the conventional and certainty-based methods tended to over-smooth the data. The task-driven reconstruction method presents a promising regularization method in MBIR by explicitly incorporating task-based imaging performance as the objective. The results demonstrate improved ICH conspicuity and support the development of high-quality CBCT systems. [ABSTRACT FROM AUTHOR]

A prototype cone-beam CT (CBCT) head scanner featuring model-based iterative reconstruction (MBIR) has been recently developed and demonstrated the potential for reliable detection of acute intracranial hemorrhage (ICH), which is vital to diagnosis of traumatic brain injury and hemorrhagic stroke. However, data truncation (e.g. due to the head holder) can result in artifacts that reduce image uniformity and challenge ICH detection. We propose a multi-resolution MBIR method with an extended reconstruction field of view (RFOV) to mitigate truncation effects in CBCT of the head. The image volume includes a fine voxel size in the (inner) nontruncated region and a coarse voxel size in the (outer) truncated region. This multi-resolution scheme allows extension of the RFOV to mitigate truncation effects while introducing minimal increase in computational complexity. The multi-resolution method was incorporated in a penalized weighted least-squares (PWLS) reconstruction framework previously developed for CBCT of the head. Experiments involving an anthropomorphic head phantom with truncation due to a carbon-fiber holder were shown to result in severe artifacts in conventional single-resolution PWLS, whereas extending the RFOV within the multi-resolution framework strongly reduced truncation artifacts. For the same extended RFOV, the multi-resolution approach reduced computation time compared to the single-resolution approach (viz. time reduced by 40.7%, 83.0%, and over 95% for an image volume of 6003, 8003, 10003 voxels). Algorithm parameters (e.g. regularization strength, the ratio of the fine and coarse voxel size, and RFOV size) were investigated to guide reliable parameter selection. The findings provide a promising method for truncation artifact reduction in CBCT and may be useful for other MBIR methods and applications for which truncation is a challenge. [ABSTRACT FROM AUTHOR]

The effects of detector readout gain mode and bowtie filters on cone-beam CT (CBCT) image quality and dose were characterized for a new CBCT system developed for point-of-care imaging of the head, with potential application to diagnosis of traumatic brain injury, intracranial hemorrhage (ICH), and stroke. A detector performance model was extended to include the effects of detector readout gain on electronic digitization noise. The noise performance for high-gain (HG), low-gain (LG), and dual-gain (DG) detector readout was evaluated, and the benefit associated with HG mode in regions free from detector saturation was quantified. Such benefit could be realized (without detector saturation) either via DG mode or by incorporation of a bowtie filter. Therefore, three bowtie filters were investigated that varied in thickness and curvature. A polyenergetic gain correction method was developed to equalize the detector response between the flood-field and projection data in the presence of a bowtie. The effect of bowtie filters on dose, scatter-to-primary ratio, contrast, and noise was quantified in phantom studies, and results were compared to a high-speed Monte Carlo (MC) simulation to characterize x-ray scatter and dose distributions in the head. Imaging in DG mode improved the contrast-to-noise ratio (CNR) by ~15% compared to LG mode at a dose (D0, measured at the center of a 16 cm CTDI phantom) of 19 mGy. MC dose calculations agreed with CTDI measurements and showed that bowtie filters reduce peripheral dose by as much as 50% at the same central dose. Bowtie filters were found to increase the CNR per unit square-root dose near the center of the image by ~5–20% depending on bowtie thickness, but reduced CNR in the periphery by ~10–40%. Images acquired at equal CTDIw with and without a bowtie demonstrated a 24% increase in CNR at the center of an anthropomorphic head phantom. Combining a thick bowtie filter with a short arc (180°  +  fan angle) scan centered on the posterior of the head reduced dose to the eye lens by up to 90%. Acquisition in DG mode (without a bowtie filter) was beneficial to the detection of small, low contrast lesions (e.g. subtle ICH) in CBCT. While bowtie filters were found to reduce dose, mitigate sensor saturation at the periphery in HG mode, and improve CNR at the center of the image, the image quality at the periphery was slightly reduced compared to DG mode, and the use of a bowtie required careful implementation of the polyenergetic flood-field correction to avoid artifacts. [ABSTRACT FROM AUTHOR]